The overall objective of this research is to probe the structure and function of microtubules in mammalian cells. Specifically, we plan to establish whether or not the carbamate herbicides isopropyl N-phenylcarbamate (IPC) and isopropyl N-(3-chlorophenyl) carbamate (CIPC) interact with and disrupt microtubles in animal cells as they do in plant cells. These studies will extend recent work with a related compound methyl-5-(thienylcarbonyl-1H-benzimidazol-2-yl) carbamate that is an extremely potent antimicrotubule agent in human leukocytes. In addition, we will test the hypothesis that microtubule assembly in vivo may be controlled by the levels and turnover of glutathione. We will continue to study the defect in Chediak-Higashi syndrome that leads to impaired microtubule assembly and defective bactericidal activity of polymorphonuclear leukocytes. Our data establishing impaired microtubule assembly in CH leukocytes provide the first genetic defect at the level of the cytoplasmic microtubule. The defect can be corrected, at last in part, by cyclic GMP and cholinergic agonists, suggesting a future clinical approach to this disorder. BIBLIOGRAPHIC REFERENCES: Berlin, R.D., J.M. Oliver, T.E. Ukena ad H.H. Yin. 1975. The Cell Surface. N. Eng. J. Med, 292: 515. Berlin, R.D. and J.M. Oliver. 1975. Membrane transport of purine and pyrimidine bases and nucleosides in animal cells. Int. Rev. Cytol. 42: 287.